An Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With TK2 Deficiency

Thymidine Kinase 2 Deficiency Clinical Trial

— Continuation  

Official title:

A Phase 2 Open-Label Study of Continuation Treatment With Combination Pyrimidine Nucleosides in Patients With Thymidine Kinase 2 Deficiency (TK2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03845712
• Other study ID #: TK0102
• Secondary ID: 2018-004277-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 5, 2019
• Est. completion date: June 18, 2025

Study information

• Verified date: November 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2 prospective open-label treatment study of the safety and efficacy of doxecitine and doxribtimine in study participants with thymidine kinase 2 (TK2) deficiency who participated in the retrospective study MT-1621-101 [NCT03701568] or who were receiving nucleos(t)ide treatment and were approved by the Sponsor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: June 18, 2025
• Est. primary completion date: June 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Signed informed consent by the parent(s) or legally authorized representative (LAR) and/or assent by the study participant (when applicable).

2. Confirmed genetic mutation in the TK2 gene.

3. Absence of other genetic disease or polygenic disease.

4. Current treatment with nucleos(t)ides for TK2 deficiency. Study participants who were not previously enrolled in MT-1621-101 [NCT03701568] will require Sponsor approval to ensure that collection of clinical and functional measurements prior to treatment are sufficient to serve as baseline assessments for purposes of evaluating safety and efficacy.

5. Female study participants must not be breastfeeding, have a negative pregnancy test at screening (females =10 years old), and have no intention to become pregnant during the course of the study. Female study participants who are of childbearing potential (ie, following menarche until =1 year post-menopausal if not anatomically and physiologically incapable of becoming pregnant) must agree and commit to the use of highly effective methods of birth control for the duration of the study and for 30 days after the end of the study. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (ie, <1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. In certain countries (if permitted by law), women of childbearing potential may instead agree to abide by heterosexual sexual abstinence during the study and for 30 days after the end of the study.

6. Male study participants with sexual partners should use condoms for the duration of the study and for 30 days after the last dose of study drug to prevent passing study drug to the partner in the ejaculate. Male participants should be advised not to donate sperm for 30 days after the last dose of study drug.

7. Willingness to maintain current treatment regimen and current exercise regimen for the duration of the clinical study.

8. Willingness to comply with the study protocol, including but not limited to, all study procedures, study visits, and study drug compliance.

Exclusion Criteria:

1. History of liver disease, or liver function test results (ALT, AST, or total bilirubin) =2× upper limit of normal without prior Sponsor approval.

2. Other significant medical condition that, in the opinion of the Investigator or Study Sponsor, may confound interpretation of the clinical course of TK2 deficiency.

Related Conditions & MeSH terms

• Thymidine Kinase 2 Deficiency

Intervention

Drug:
• doxecitine and doxribtimine
Doxecitine and doxribtimine is administered orally in 3 equal doses given approximately 6 to 8 hours apart. Doxecitine and doxribtimine is administered with food.

Locations

Country	Name	City	State
Israel	Tk0102 4038	Haifa
Israel	Tk0102 4039	Holon
Israel	Tk0102 4037	Nehariya
Spain	Tk0102 3102	Barcelona
Spain	Tk0102 3121	Esplugues de Llobregat
Spain	Tk0102 3031	Madrid
Spain	Tk0102 3101	Sevilla
United States	Tk0102 1005	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES, Inc.

Countries where clinical trial is conducted

United States,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as adverse events (AEs): number of participants who experience adverse events	Safety as determined by the number of participants who experience adverse events (AE), type of AE, severity of AE.	Approximately 3 years
Primary	Safety as determined by laboratory measurements	Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests.	Approximately 3 years
Primary	Safety as determined by electrocardiograms (ECGs)	Number of Participants Who Experience a Clinically Significant Change from Baseline ECG.	Approximately 3 years
Secondary	Efficacy - Motor Function Assessments	Patient or physician reported achievement (capable) or loss (not capable) of gross motor milestones.	Approximately 3 years
Secondary	Efficacy - Respiratory Status	Pulmonary Function Tests (PFTs).	Approximately 3 years
Secondary	Efficacy - Growth/Nutrition	Growth in patients over time compared to normals using the WHO reference standards and expressed as Z scores.	Approximately 3 years
Secondary	Efficacy - Growth/Nutrition	Requirement for supplemental feeding/feeding tube within 1 patient over time and time to change of status of use of supplemental feeding/feeding tube (tube inserted for feeding use vs tube removed).	Approximately 3 years
Secondary	Maximum plasma concentration (Cmax) of deoxycytidine and deoxythymidine	PK of dC and dT (Cmax - peak plasma concentration)	Approximately 3 years
Secondary	Time to maximum plasma concentration (Tmax) of deoxycytidine and deoxythymidine	PK of dC and dT (Tmax - time to maximum plasma concentration)	Approximately 3 years
Secondary	AUC - area under the plasma concentration time curve of deoxycytidine and deoxythymidine	PK of dC and dT (AUC - area under the plasma concentration time curve)	Approximately 3 years
Secondary	Apparent elimination half-life (t1/2) of deoxycytidine and deoxythymidine	PK of dC and dT (t1/2 - apparent elimination half-life)	Approximately 3 years
Secondary	Biomarkers (plasma from blood)	Biomarkers which may be related to TK2 disease and/or drug treatment (eg, number of participants with normal vs abnormal creatine kinase measured in u/l compared to normal ranges).	Approximately 3 years
Secondary	Biomarkers (plasma from blood)	Biomarkers which may be related to TK2 disease and/or drug treatment (eg, number of participants with normal vs abnormal lactate levels measured in mmol/l compared to normal ranges).	Approximately 3 years
Secondary	Quality of life through patient questionnaire - Individualized Neuromuscular Quality of Life (INQoL)	INQOL Questionnaire with 15 questions in 3 sections about muscle weakness, pain, fatigue, locking of muscles, droopy eyelids, vision, swallowing, daily activity, independence, relationships, feelings, appearance, and treatment where patients aged 12 years and older rate how they feel and their muscles function to accomplish daily activities on a scale of 0 to 7, where lower values are generally associated with a better outcome.	Approximately 3 years
Secondary	Characterization of health care utilization		Approximately 3 years
Secondary	Efficacy Assessment: Clinical Global Impression of Improvement (CGI-I) and Patient Global Impression of Improvement (PGI-I)	Clinical Global Impression of Improvement (CGI-I) completed by Investigator and Patient Global Impression of Improvement (PGI-I) completed by the patient/caregiver.	Approximately 3 years